One of the most striking effects reported by male and female users of methamphetamine, a highly addictive psychostimulant drug of abuse, is an increase in sexual libido and an insatiable need and urgency for sex. In addition, female methamphetamine users are more likely to engage in risky sexual behavior compared to female users of other psychostimulant drugs such as cocaine and amphetamine. The proposed work will examine the molecular underpinnings of the facilitation of motivated sexual behavior in the female rat by methamphetamine. Specifically, this proposal focuses on the medial amygdala, which receives dopaminergic input from the VTA. The medial amygdala has been shown to be a pivotal motivational area and sexual center in the brain. The specific aims of this proposal are to test the role of the medial amygdala in the activation of the female sexual circuitry by methamphetamine and to test the role of dopamine in the medial amygdala in mediating the enhancement in sexual motivation. This research will be conducted in hormonally-primed female rats, or oil-treated controls, that have been treated with methamphetamine or saline vehicle. We will utilize molecular and cellular techniques of immunocytochemistry, real-time RT-PCR, in addition to microinfusion of pharmacological blockers to dopamine or glutamate receptors and lesion studies. These aims will provide information regarding the actions of the neurotransmitter systems potentially underlying this enhancement of sexual motivation, which could have implications for the treatment of methamphetamine addiction via pharmacological agents. The potential findings of this research will advance our understanding of drugs of abuse in the induction of sexual drives and behavior, which could have important implications in terms of risky sexual behavior and disease transmission. Methamphetamine use in this country, from the urban centers to the rural towns, is becoming an epidemic that disrupts the family, the community, and society as a whole. One of the motivations for the use of methamphetamine is that it dramatically increases sexual libido, which has been linked to a rise in the rate of sexually transmitted diseases and unplanned pregnancies. This proposal, which seeks to understand the ways methamphetamine increases sexual motivation, may be useful in providing an avenue to combat methamphetamine addiction.